Nitrogen monoxide (hereinafter abbreviated as NO) has been widely studied in various fields such as applications to control physiological functions, clinical episodes, and therapy. In particular, in ischemic disorders or at the time of organ transplantation, various disorders are caused by endogenous reduction in NO production due to substrate depletion accompanying blood flow decrease, so that exogenous NO supplementation (called NO supplementation therapy) is indispensable. Although among others NO inhalation therapy has been tried as the NO supplementation therapy, the current situation is that NO disappears in an extremely short time in a living organism and selective obtention of advantageous effects is difficult because of NO itself having high reactivity and diversity (Ignarro L. J. et al., Pharm Res., 1989, 6, 651-659).
NO is known to react, in a living organism, with a trial group (hereinafter, abbreviated as an SH group) of a protein or the like and converted into S-nitrosothiol (hereinafter, abbreviated as RS—NO), which maintains a relatively stable state and functions as an NO reservoir, thus participating in control of NO concentration in the living organism (Ignarro L. J. et al., J. Pharmacol. Exp. Ther., 1981, 218 739-749).
Usefulness of nitrosylated proteins has been reported. Analyses on the efficiency of nitrosylation and antibacterial activity of various bacteria-infected model animals using albumin variants having a mutation in one or more amino acid residues in the constituent amino acid sequences indicated that the albumin variants are efficiently nitrosylated and the nitrosylated products exhibit more potent antibacterial activity than NO and low molecular weight nitrosothiol (JP 2005-206577 A, US2005/0222026).
On the other hand, albumin can be used as an NO transport protein. In spite of having a free cysteine residue at the 34th position, albumin is known to have only a low reactivity, so that attempts to allow albumin and an NO donor to react to promptly obtain S-nitrosylated albumin fail. Then, to add NO to albumin, a method is known in which the binding efficiency is increased by adding a suitable chemical modulator to albumin or the reaction efficiency is increased by mutating a part of amino acids of albumin to cysteine. These methods involve changing the inherent structure of albumin, which causes the problem that the behavior of albumin in the living organism may be changed.